Additional evidence for a possible link between breastfeeding and colorectal cancer (CRC) was found in a large cohort study.
In two prospective cohorts of 158,696 women followed for more than 20 years, being breastfed in infancy was associated with a 23% increased risk of CRC in adulthood (HR 1.23, 95% CI 1.10-1.38, P<0.001), Chen Yuan, ScD, of the Dana-Farber Cancer Institute in Boston, and colleagues reported in .
CRC risk increased with the duration of breastfeeding, from 14% higher for individuals breastfed 3 months or less and 36% higher for those breastfed 9 months or more (P<0.001 for trend). The study also found significantly higher risk among participants age 55 or younger (HR 1.38, 95% CI 1.06-1.80).
Yuan's group emphasized, however, that the associations they found do not establish causation. "Our study does not serve as a discouragement of breastfeeding," the researchers wrote, "but rather highlights the pressing need to investigate the underlying mechanisms and explore potential interventions. Breastfeeding has well-established and essential benefits that likely outweigh any potential increased risk of CRC in adulthood."
A spokesperson for the American Gastroenterological Association who was not involved in the study agreed with the authors on that point. In an email to Ƶ, C. Richard Boland, MD, noted that overall health outcomes were not established in the breast-fed versus the non-breast-fed groups.
"I think that the overall impact on health might be more complicated than just the CRC risk," Boland said. "So, I would not advocate for reducing breast-feeding of infants at this time. I would require more confirmatory information."
Previous studies have reported similar results, Yuan and colleagues noted, and there are several hypotheses about the possible breastfeeding-CRC link. One long-standing but controversial hypothesis is that human milk may contain a virus similar to the mouse mammary tumor virus, which could be transmitted to offspring and increase their risk of cancer.
Breastfeeding has also been shown to influence gut microbiota, and there is growing evidence that the gut microbiome plays a role in CRC development. Additionally, the lower risk of CRC in non-breastfed individuals may be linked to the potential benefits of cow's milk and formula fortified with vitamins and minerals.
"While consuming specific vitamins and minerals, such as vitamin D, in adulthood has been associated with decreased risk of colorectal neoplasia, including young-onset CRC, the effects of consuming these nutrients during early life are poorly understood," Yuan and co-authors explained.
They prospectively analyzed data from participants in the Nurses' Health Study, which included 66,634 women ages 46-93, and the Nurses' Health Study II, which included 92,062 woman ages 27-68. During 3.5 million person-years of follow-up, the researchers identified 1,490 incident cases of CRC.
The team used Cox regression and logistic regression to investigate associations between having been breastfed and CRC risk. The researchers adjusted for potential CRC risk factors including body mass index, family history of CRC, inflammatory bowel disease, diabetes, aspirin use, menopausal status, hormone therapy, physical activity, smoking, alcohol intake, and other dietary factors.
The study also found that breastfeeding was linked with pre-cancerous conditions: a relative 46% greater risk for high-risk adenomas in individuals younger than 50 (OR 1.46, 95% CI 1.16-1.83), and 16% higher risk for serrated polyps in those older than 50 (OR 1.16, 95% CI 1.07-1.25).
In the U.S., breastfeeding rates declined to a low of less than 30% from the early 20th century to the 1960s, and then rebounded and reached more than 60% in the 1990s as public perception of breastfeeding changed. The incidence of CRC has risen significantly among individuals age 50 and younger since the mid-1990s and among those ages 50 to 64 since 2011, Yuan and co-authors noted.
"These shifting patterns reflect increased CRC risk in generations born after 1950-1960 and decreased risk in previous generations, implying that population-level changes in early-life exposures may be contributing to the trend," the team wrote.
The primary analysis relied on self-reported history of being breastfed, which is subject to error, the researchers noted. However, they validated their findings in a subset of 39,683 participants from the Nurses' Mothers' Study, where the mothers reported on whether they breastfed their daughters.
Another potential limitation was that the study population consisted primarily of white females, so the results might not be generalizable to men or other racial or ethnic groups, Yuan and colleagues said.
Disclosures
The study was supported by the NIH.
Yuan reported no conflicts of interest; co-authors reported financial relationships with Bayer, Boehringer Ingelheim, Pfizer, Janssen, GSK, Vertex, Pharmavite, and CytomX.
Primary Source
Clinical Gastroenterology and Hepatology
Yuan C, et al "Being breastfed in infancy and risk of colorectal neoplasia" Clin Gastroenterol Hepatol 2023; DOI: 10.1016/j.cgh.2023.08.023.